Schizophrenia is a complex mental disorder typically appearing in late adolescence or early adulthood with a world-wide prevalence of approximately 1% of the adult population, which has enormous social and economic impact. The criteria of the Association of European Psychiatrists (ICD) and the American Psychiatric Association (DSM) for the diagnosis of schizophrenia require two or more characteristic symptoms to be present: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior (positive symptoms), or negative symptoms (alogia, affective flattening, lack of motivation, anhedonia). As a group, people with schizophrenia have functional impairments that may begin in childhood, continue throughout adult life and make most patients unable to maintain normal employment or otherwise have normal social function. They also have a shortened lifespan compared to the general population, and suffer from an increased prevalence of a wide variety of other neuropsychiatric syndromes, including substance abuse, obsessive-compulsive symptoms and abnormal involuntary movements prior to antipsychotic treatment. Schizophrenia is also associated with a wide range of cognitive impairments, bipolar disorders, major depression and anxiety disorders, the severity of which limits the functioning of patients, even when psychotic symptoms are well controlled. The primary treatment of schizophrenia is antipsychotic medications. Antipsychotics, for example risperidone, olanzapine, however, fail to significantly ameliorate the negative symptoms and cognitive dysfunction.
Antipsychotic drugs have shown clinical efficacy for the treatment of the following diseases:
Fibromyalgia, which is a syndrome characterized by chronic generalized pain associated with different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems, hypersensitivity to physical and psychological environmental stimuli, depression and anxiety (CNS Drugs, 2012, 26(2): 135-53).
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Compounds structurally similar to those described herein are shown in WO2007063925 (Astellas Pharma/Japan), wherein the described active compounds have a NHR-substitution on the left phenyl or heteroaryl group, for the treatment of pain; WO0056709 and WO0008202 (Sugen, Inc./USA) describe compounds without substitution on the 2-oxo-2,3-dihydro-indol ring for the treatment of cancer, hepatitis, ocular diseases and cardiovascular diseases; DE 3925584, EP0344634, DE 3803775, U.S. Pat. No. 4,835,280, U.S. Pat. No. 4,810,801, DE 3501497, EP0161632 and DE 3417643 (Boehringer Mannheim/DE) describe 2-oxo-2,3-dihydro-indol derivatives without substitution in 1-position (N-atom) for use as intermediates or for the treatment of heart and circulatory diseases, for influencing thrombocyte function and for the treatment of cardiovascular diseases.